The pharmacological effects of histamine on, for example, the cardiovascular system, gastric secretion and smooth muscle of mammals presumably reflect physiological roles which are now only poorly defined. This project attempts to examine these roles through a study of the distribution, kinetic and physicochemical properties, and regulatory mechanism of histidine decarboxylase, the enzyme responsible for the biosynthesis of histamine. The enzyme's substrate and coenzyme, histidine and pyridoxal-P, cyclize nonenzymatically to form an addition compound which is probably not decarboxylated; the effect of this previously overlooked reaction on enzyme activity will be determined in addition to standard kinetic and physico-chemical analyses. Affinity chromatography based on coenzyme, substrate-coenzyme or substrate analogues will be used for purification. Histidine decarboxylase is in some sense an adaptive enzyme; if possible, this control mechanism will be examined both in vitro and in vivo.